Bimodal effect of oxytocin on avoidance behavior may be caused by the presence of two peptide sequences with opposite action in the same molecule.

Oxytocin (OXT) reduced locomotion, rearing, grooming and bolus production in a circular open field at 15 min, but not at 60 min, after a subcutaneous (s.c.) injection. The OXT fragments OXT-(1-8), OXT-(4-9), OXT-(4-8), OXT-(5-9) and OXT-(5-8) had no effect at 15 min or 60 min after s.c. injection. OXT and its fragments attenuated passive avoidance behavior following postlearning (consolidation test) or preretention (retrieval test) injection. Some of the fragments were more potent than the parent molecule. The extinction of pole-jumping avoidance behavior was inhibited by OXT-(1-9) in doses of 1 and 3 micrograms s.c. Doses lower than 1 microgram had no effect or even tended to facilitate extinction. This bimodal effect was more pronounced when OXT fragments OXT-(4-9) and OXT-(5-9) were used. S.c. injection of these peptides in low doses (0.01-0.001 microgram) caused facilitation, and in doses higher than 0.1 microgram inhibition, of pole-jumping avoidance behavior. Removal of the Gly9-NH2 moiety eliminated the bimodal effect; such peptides (OXT-(1-8), OXT-(4-8), OXT-(5-8) caused facilitation of extinction only. Since the C-terminal peptides Pro-Leu-Gly-NH2 and Leu-Gly-NH2 both seem to inhibit extinction of pole-jumping avoidance behavior, it is possible that there are two sequences in the OXT molecule, which act in opposite ways.